The goal of the proposed Conte Center for the Neuroscience of Mental Disorders (CCNMD), The Neurobiology of Stimulus Encoding in Schizophrenia, is to integrate basic and clinical neuroscience research in a cohesive effort to help elucidate neural substrates of schizophrenia. We will pursue a unifying hypothesis to be tested with converging multidisciplinary approaches, with the potential of contributing a new understanding of the symptoms, pathophysiology and etiology of schizophrenia. Perception, attention, working memory, and learning represent a continuum of information processing in which deficits have been reported in schizophrenia. Such deficits span sensory modalities and thus may reflect a fundamental disturbance in neurobiological mechanisms by which the brain responds to and changes with environmental input. The hypothesis of the proposed Center is that abnormal neural plasticity is a core neurobiological feature of schizophrenia related to deficits in the stimulus processing continuum. Abnormal plasticity is manifested in impaired sensory gating and the ensuing failure to encode salient stimulus features. To test this hypothesis, parallel experiments will characterize the stimulus processing deficits of schizophrenia and their modeled counterparts in mice, with a focus on gating and encoding of auditory and visual input. The neurobiological mechanisms that may account for these deficits will be investigated at complementary levels - anatomic, metabolic, electrophysiological, pharmacological, local circuit, cellular, and molecular. The Center will be organized into six Projects - I. Electrophysiology; II. fMRI; III. Signaling; IV. Intracellular; V. Cellular/Molecular; VI. Computation - that will be supported by two Cores - A. Coordination and B. Data and Biostatistics. The Center capitalizes on the collaborative expertise of investigators and resources at the University of Pennsylvania for conducting this challenging research. In addition to advancing its scientific agenda, the Center will be an educational resource for faculty, fellows, residents, graduate and undergraduate students. It will also be a clinical and educational resource for individuals with schizophrenia, their families and care providers.